Extrusion process for coating stents

ABSTRACT

The present invention provides a method of coating a stent. A stent framework is provided. A polymeric mixture is injected through at least one inlet port in an extrusion die, and the polymeric mixture is extruded through a shaped orifice onto at least a portion of the stent framework to form a coated stent. A coated stent including an extruded coating disposed on at least a portion of the stent framework and a system for treating a vascular condition are also disclosed.

RELATED APPLICATIONS

This application is a Division of and claims the benefit of U.S. patentapplication Ser. No. 10/636,865 filed Aug. 7, 2003.

FIELD OF THE INVENTION

This invention relates generally to biomedical stents. Morespecifically, the invention relates to an extruded coating disposed onan endovascular stent, and methods of coating thereof.

BACKGROUND OF THE INVENTION

Extrusion processes have long been used to coat numerous items such aspipes, cables and wires with various plastics. Conventional extrusionprocesses use a chamber to hold the material used for extrusion.Mechanical pressure is applied via a compression ram at one end of thechamber, and the material is forced through a patterned opening at theother end to create an extruded form or a coating over an item. Forexample, a copper wire can be coated with a process that extrudes apolymer from an extrusion die, drawing the polymer onto the wire in avacuum environment, and applying the polymer to the wire inside theannular extrudate or melt cone.

Extrusion methods have been used to create coatings, sheaths or tubingfor protecting or deploying various medical devices that use wires. Oneexample of an extruded polymeric sheath for coating wires is describedin “Co-Extruded, Multi-Lumen Medical Lead,” Borgersen et al., U.S.Patent Publication 2002/0183824 issued Dec. 5, 2002. The electricallyinsulating sheath can be used with, for example, implantable cardiacleads for delivering pacing pulses and defibrillation shocks, or sensinga cardiac electrogram (EGM). The body sheath is co-extruded in aco-extrusion process with materials of differing durometers in differingaxial sections thereof to create a unitary body sheath. Another methodfor extruding material onto a wire is described by Solar and others in“Method of Manufacturing a Guidewire with an Extrusion Jacket”, U.S.Patent Publication 2002/0084012 issued Jul. 4, 2002. A corewire is fedinto an extrusion device and a material is extruded onto the corewirewhile a gripping apparatus pulls the corewire through the extrusiondevice to create a coating or extrusion jacket.

Extruded polymeric tubing has been used for medical grafts. An exampleof a medical graft that has an additional exterior support structure isdisclosed in “Endoluminal Graft with Integral Structural Support andMethod for Making Same”, Edwin et al., U.S. Pat. No. 6,053,943 issuedApr. 25, 2000. The structurally supported tubular graft may include aspiraling beading element that is co-extruded with the supportstructure. The spiraling support structure, which is on the outside ofthe graft, allows for the expansion of the graft. Unconnected ends ofthe support structure may have outwardly protruding barbs that uponexpansion of the graft secure the graft within a blood vessel or bodylumen. The support structure is designed to constrain the tubing of thegraft.

An extruded sheath assembled with an expandable stent may be used toconstrain the stent until it has reached its areas of deployment. Onesuch sheath is described in “Methods of Forming a Coating for aProsthesis”, Harish et al., U.S. Patent Publication 2002/0122877 issuedSep. 5, 2002. The sheath can be used to constrain an expandable stentuntil it has reached its areas of deployment. The method formanufacturing the associated stent assembly includes steps of forming asheath, placing the sheath upon an implantable device or endoluminalprosthesis, and heating the sheath to coat the device or prosthesis. Thecoating created from the sheath may be used for the delivery of anactive ingredient and may have a selected pattern of interstices forallowing a fluid to seep through the coating in the direction of thepattern created.

There are a number of dipping and spraying methods that have been usedto apply coatings to the stent framework. A less common method usesinjection molding, one example being described in “Polymer-Coated StentStructure”, Loeffler, U.S. Pat. No. 5,897,911 issued Apr. 27, 1999. Anexterior mold around the stent controls the thickness of polymer on theexterior surface of the stent. Alternatively, this method may use apreformed sheath of polymer fitted to the interior of the stent wherebya subsequent application of a polymer coats the exterior of the stent.

Although extrusion methods have been developed to extrude coatings onmedical devices such as electrical leads and guidewires, little researchhas focused on the extrusion of a polymeric or drug-polymer coating ontoa stent framework. Recent clinical studies on drug-coated vascularstents indicate much therapeutic benefit with the addition of stentcoatings that contain pharmaceutical drugs. These drugs may be releasedfrom the coating while in the body, delivering their patent effects atthe site where they are most needed. Thus, the localized levels of themedications can be elevated, and therefore potentially more effectivethan orally- or intravenously-delivered drugs that distribute throughoutthe body.

It would be desirable to have a process for coating and covering a stentwith a wide variety of polymers, drugs, and other types of coatingmaterials. The desired process may not require heating and wouldtherefore have minimal impact on pharmaceutical drugs and compoundsincorporated into the stent coating. The desired process would uselittle, if any, solvent, and reduce the amount of drug wasted duringtypical dipping and spraying cycles. The process would require fewerundesirable chemicals, and reduce or eliminate drying time needed forevaporation of a solvent. The process would allow large quantities ofdrugs to be included in the coating, and allow various forms of drugssuch as micronized powdered drugs and encapsulated drug microspheres tobe included within the coating. The method would provide awell-controlled coating thickness, allow a large percentage of drugswithin the coating, require little time for application of the desiredcoating, and overcome the deficiencies and limitations of other coatingmethods described above.

SUMMARY OF THE INVENTION

One aspect of the invention provides a method of coating a stent. Astent framework is provided. A polymeric mixture is injected through atleast one inlet port in an extrusion die, and the polymeric mixture isextruded through a shaped orifice of the extrusion die onto at least aportion of the stent framework to form a coated stent.

Another aspect of the invention provides a coated stent including astent framework and an extruded coating disposed on at least a portionof the stent framework.

Another aspect of the invention provides a system for treating avascular condition, including a catheter and a drug-polymer coated stentcoupled to the catheter. The drug-polymer coated stent includes a stentframework and a drug-polymer coating disposed on the stent framework,wherein the drug-polymer coating is extruded onto at least a portion ofthe stent framework.

The present invention is illustrated by the accompanying drawings ofvarious embodiments and the detailed description given below. Thedrawings should not be taken to limit the invention to the specificembodiments, but are for explanation and understanding. The detaileddescription and drawings are merely illustrative of the invention ratherthan limiting, the scope of the invention being defined by the appendedclaims and equivalents thereof. The foregoing aspects and otherattendant advantages of the present invention will become more readilyappreciated by the detailed description taken in conjunction with theaccompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

Various embodiments of the present invention are illustrated by theaccompanying figures, wherein:

FIG. 1 is an illustration of a system for treating a vascular conditionincluding a drug-polymer coated stent coupled to a catheter, inaccordance with one embodiment of the current invention;

FIG. 2 is a cross-sectional view of a drug-polymer coated stent, inaccordance with one embodiment of the current invention;

FIG. 3 is a cross-sectional view of a coated stent, in accordance withone embodiment of the current invention;

FIG. 4 is a cross-sectional view of a system for coating a stent, inaccordance with one embodiment of the current invention;

FIG. 5 is a cross-sectional view of a system for coating a stent, inaccordance with another embodiment of the current invention;

FIG. 6 is a cross-sectional view of a system for coating a stent, inaccordance with another embodiment of the current invention; and

FIG. 7 is a flow diagram of a method for coating a stent, in accordancewith one embodiment of the current invention.

DETAILED DESCRIPTION OF THE PRESENTLY PREFERRED EMBODIMENTS

FIG. 1 shows an illustration of a system for treating a vascularcondition, comprising a drug-polymer coated stent coupled to a catheter,in accordance with one embodiment of the present invention at 100.Coated stent with catheter 100 includes a drug-polymer coated stent 120coupled to a delivery catheter 110. Drug-polymer coated stent 120includes a stent framework 130 and an extruded drug-polymer coating 140disposed on stent framework 130. Extruded drug-polymer coating 140 isextruded onto at least a portion of the stent framework, such as aninner surface 132 of stent framework 130, an outer surface 134 of stentframework 130, or both inner surface 132 and outer surface 134 of stentframework 130. Extruded drug-polymer coating 140 comprises adrug-polymer and at least one therapeutic agent. Openings or apertures136 between struts and elements of stent framework 130 are generallyopen and free of drug-polymer, though in some cases, drug-polymercoating 140 covers apertures 136, forming what is sometimes referred toas a covered stent.

Insertion of coated stent 120 into a vessel of a body helps treat, forexample, heart disease, various cardiovascular ailments, and othervascular conditions. Catheter-deployed coated stent 120 typically isused to treat one or more blockages, occlusions, stenoses or diseasedregions in the coronary artery, femoral artery, peripheral arteries, andother arteries in the body. Treatment of vascular conditions may includethe prevention or correction of various ailments and deficienciesassociated with the cardiovascular system, the cerebrovascular system,urinogenital systems, biliary conduits, abdominal passageways and otherbiological vessels within the body.

An exemplary drug-polymer coating 140 includes or encapsulates one ormore therapeutic agents. Extruded drug-polymer coating 140 may compriseone or more therapeutic agents dispersed within or encased bydrug-polymer layers on coated stent 120, which are eluted from coatedstent 120 with controlled time delivery after the deployment of coatedstent 120 into the body. A therapeutic agent is capable of producing abeneficial effect against one or more conditions including coronaryrestenosis, cardiovascular restenosis, angiographic restenosis,arteriosclerosis, hyperplasia, and other diseases or conditions. Forexample, the therapeutic agent can be selected to inhibit or preventvascular restenosis, a condition corresponding to a narrowing orconstriction of the diameter of the bodily lumen where the stent isplaced. Extruded drug-polymer coating 140 may comprise, for example, anantirestenotic drug such as rapamycin, a rapamycin analogue, or arapamycin derivative to prevent or reduce the recurrence or narrowingand blockage of the bodily vessel. Drug-polymer coating 140 may comprisean anti-cancer drug such as camptothecin or other topoisomeraseinhibitors, an antisense agent, an antineoplastic agent, anantiproliferative agent, an antithrombogenic agent, an anticoagulant, anantiplatelet agent, an antibiotic, an anti-inflammatory agent, asteroid, a gene therapy agent, an organic drug, a pharmaceuticalcompound, a recombinant DNA product, a recombinant RNA product, acollagen, a collagenic derivative, a protein, a protein analog, asaccharide, a saccharide derivative, a bioactive agent, a pharmaceuticaldrug, a therapeutic substance, or a combination thereof.

The elution rates of the therapeutic agents and total drug eluted intothe body and the tissue bed surrounding the stent framework are based onthe thickness of extruded drug-polymer coating 140, the constituency ofdrug-polymer coating 140, the nature and concentration of thetherapeutic agents, the thickness and composition of any cap coat, andother factors. Extruded drug-polymer coating 140 may include and elutemultiple therapeutic agents to achieve the desired therapeutic effect.Drug-polymer coating 140 can be tailored to control the elution of oneor more therapeutic agents, primarily by diffusion processes. In somecases, a portion of drug-polymer coating 140 dissolves and is absorbedinto the body, releasing therapeutic agents from within the coating asthe therapeutic agents are exposed to the surrounding tissue bed orbodily fluids flowing through the coated stent. In other cases,drug-polymer coating 140 erodes from coated stent 120 to release thetherapeutic compounds, the residual polymer being expelled by the body.

Incorporation of a drug or other therapeutic agent into extrudeddrug-polymer coating 140 allows, for example, the rapid delivery of apharmacologically active drug or bioactive agent within twenty-fourhours following the deployment of a stent, with a slower, steadydelivery of a second bioactive agent over the next three to six months.For example, a first therapeutic agent may comprise an antirestenoticdrug such as rapamycin, a rapamycin analogue, or a rapamycin derivative.The second therapeutic agent may comprise, for example, an anti-cancerdrug such as camptothecin or other topoisomerase inhibitors. Thetherapeutic agent constituency in the extruded drug-polymer coating maybe, for example, between 0.1 percent and 50 percent or more of thedrug-polymer coating by weight.

Catheter 110 of an exemplary embodiment of the present inventionincludes a balloon 112 that expands and deploys the stent within avessel of the body. After positioning coated stent 120 within the vesselwith the assistance of a guide wire traversing through a guidewire lumen114 inside catheter 110, balloon 112 is inflated by pressurizing a fluidsuch as a contrast fluid that fills a tube inside catheter 110 andballoon 112. Coated stent 120 is expanded until a desired diameter isreached, and then the contrast fluid is depressurized or pumped out,separating balloon 112 from coated stent 120 and leaving coated stent120 deployed in the vessel of the body. Alternatively, catheter 110 mayinclude a sheath that retracts to allow expansion of a self-expandingversion of coated stent 120.

FIG. 2 shows a cross-sectional view of a drug-polymer coated stent, inaccordance with one embodiment of the present invention at 200. Adrug-polymer coated stent 220 includes a stent framework 230 with anextruded drug-polymer coating 240. In the embodiment illustrated,drug-polymer coating 240 completely jackets or encapsulates an innersurface 232 and an outer surface 234 of stent framework 230. Apertures236 between elements of stent framework 230 are filled with drug-polymercoating 240 to form a covered stent. In other embodiments, drug-polymercoating 240 may cover the inner diameter of stent framework 230, ordrug-polymer coating 240 may wrap over outer surface 234 of stentframework 230. In other embodiments, drug-polymer coating 240 may besubsequently removed from a plurality of apertures 236 within stentframework 230 using, for example, a cutting laser or jets of hot gas.

FIG. 3 shows a cross-sectional view of a coated stent, in accordancewith one embodiment of the present invention at 300. Coated stent 320includes a stent framework 330 and an extruded stent coating 340disposed on at least a portion of stent framework 330. Stent coating 340includes a drug-polymer 344 with at least one therapeutic agent 346, andmay include a primer coating 342 positioned between drug-polymer 344 andstent framework 330. Stent coating 340 may include a cap coating 348positioned on drug-polymer 344. One or more of primer coating 342,drug-polymer 344 or cap coating 348 may be extruded onto stent framework330.

Stent framework 330 comprises a metallic or polymeric base. Materialssuch as stainless steel, nitinol, tantalum, MP35N alloy, platinum,titanium, a chromium-based alloy, a cobalt-based alloy, a suitablebiocompatible alloy, a suitable biocompatible material, a biocompatiblepolymer, or a combination thereof are used to form stent framework 330.

Primer coating 342 is used when needed to improve adhesion betweendrug-polymer 344 and stent framework 330, particularly when stentframework 330 comprises a metal such as stainless steel. Primer coating342 may be applied onto at least a portion of stent framework 330 usingapplication techniques such as dipping, spraying, brushing, painting, orextruding. Primer coating 342 may comprise primer-coating materials suchas parylene, polyurethane, phenoxy, epoxy, polyimide, polysulfone, orpellathane.

Drug-polymer 344 comprises an interspersing or encapsulation of at leastone polymer and at least one therapeutic agent 346. Polymers such aspoly(vinyl alcohol) (PVA), poly(ethylene-vinyl acetate) (PEVA),polyurethane (PU), polycaprolactone (PCL), polyglycolide (PGA),poly(lactide-co-glycolide) (PLGA), poly(ethylene oxide) (PEO),poly(vinyl pyrrolidone) (PVP), a thermoplastic polymer, a thermosetpolymer, a biostable polymer, a biodegradable polymer, a blendedpolymer, or a combination thereof may be used with one or moretherapeutic agents 346 such as camptothecin, rapamycin, a rapamycinanalog, or an anti-inflammatant to form drug-polymer 344. Drug-polymer344 may be applied onto at least a portion of stent framework 330 usingapplication techniques such as dipping, spraying, brushing, painting, orextruding. Techniques such as dipping, spraying, brushing and paintinggenerally require dissolving or suspending the drug-polymer into asuitable solvent, applying the drug-polymer solution, and drying off thesolvent. Extrusion processes allow drug-polymer 344 to be hot formed orcold formed, using polymeric and therapeutic feedstock in various formssuch as powders, granules, spheres, pellets, beads, bars, rods, one-partuncured polymers, two-part uncured polymers, and viscous liquids. Withextrusion processes, the polymer material may be cross-linked prior toapplication or after coating, providing additional flexibility in thepolymers and therapeutic compounds available for application.

Cap coating 348 can provide protection for underlying drug-polymer 344or provide an additional barrier for controlling the time-releasecharacteristics of encapsulated therapeutic agents 346. Cap coating 348may be applied onto at least a portion of stent framework 330 usingapplication techniques such as dipping, spraying, brushing and painting,or by extruding. Cap coating materials such as polyurethane orpolycaprolactone may be applied by extruding.

FIG. 4 shows a cross-sectional view of a system for coating a stent, inaccordance with one embodiment of the present invention at 400. Coatingsystem 400 includes an extrusion die 450 having at least one inlet port452 and a shaped orifice 454. A polymeric mixture 442 is injectedthrough inlet port 452, through shaped orifice 454, and onto at least aportion of a stent framework 430 to apply a stent coating 440 onto stentframework 430. In one example, injected polymeric mixture 442 comprisesa primer coating material. In another example, injected polymericmixture 442 comprises a drug-polymer. In another example, injectedpolymeric mixture 442 comprises a cap coating material.

Polymeric mixture 442 comprises at least one polymer and possibly one ormore therapeutic agents. Therapeutic agents in a suitable form such asmicronized particles, powder, granules, spheres, pellets or tablets, andthe polymer in a suitable form such as powder, granules, spheres,pellets, blocks, rods or billets are combined to form polymeric mixture442. Grinding the therapeutic agents and polymer together may help tomore evenly distribute the two within polymeric mixture 442. Compatiblesolvents may be added to polymeric mixture 442 prior to extrusion forsolvating the polymers and therapeutic agents.

The process of extruding stent coating 440 begins with insertingpolymeric mixture 442 as feedstock into a commercial extrusion machine,optionally heating polymeric mixture 442, and then forcing polymericmixture 442 under pressure onto stent framework 430. Polymeric mixture442 is injected into inlet port 452 of extrusion die 450 using anyconventional extrusion feed system such as a ram, a screw, or areciprocating plunger.

Extruded stent coatings 440 are applied to stent framework 430 bypassing stent framework 430 through shaped orifice 454 of extrusion die450 to extrude polymeric mixture 442 onto stent framework 430. Polymericmixture 442 may be extruded onto an inner surface 432 of stent framework430. Polymeric mixture 442 may be extruded onto an outer surface 434 ofstent framework 430. In the embodiment shown, stent coating 440 isextruded onto stent framework 430, encapsulating stent framework 430 andforming a covered stent with apertures 436 that are substantially filledwith stent coating material.

Shaped orifice 454 may form an annulus, with an outer dimension 456corresponding to the target outer diameter of stent coating 440, and aninner dimension 458 corresponding to the target inner diameter of stentcoating 440. A stent framework 430 is loaded into extrusion die 450, andpushed or pulled through shaped orifice 454 of extrusion die 450 to forman extruded stent coating 440 on stent framework 430.

An optional heater 460, which may be integrally formed with extrusiondie 450 or wrapped around extrusion die 450, heats polymeric mixture 442above an extrusion temperature while polymeric mixture 442 is extrudedthrough shaped orifice 454.

By using additional extrusion die 450 with different outer dimensions456 and inner dimensions 458, various primer coatings, drug-polymers,and cap coatings can be extruded onto stent framework 430 in multipleextrusion sequences, or combined with conventional dipping, brushing,spraying or painting sequences to form the desired coating matrix.Coated stents may undergo further processing steps that remove extrudedpolymeric mixture 442 from a plurality of apertures within stentframework 430.

FIG. 5 shows a cross-sectional view of a system for coating a stent, inaccordance with another embodiment of the present invention at 500.Coating system 500 allows for semi-continuous feeding of stentframeworks to form covered or coated stents 520. Coating system 500includes an extrusion die 550 having at least one inlet port 552 and ashaped orifice 554. A series of stent frameworks 530 may be placed on amandrel or support wire 562 prior to extruding a polymeric mixture 542.An inner surface 532 of stent framework 530 contacts an outer surface ofmandrel or support wire 562 to allow extrusion of polymeric mixture 542onto at least an outer surface 534 of stent framework 530. Outer surface534 of stent framework 530 is coated.

Polymeric mixture 542 is injected through inlet port 552, through shapedorifice 554, and onto at least a portion of a stent framework 530 toapply an extruded stent coating 540 onto stent framework 530. In oneexample, injected polymeric mixture 542 comprises a primer coatingmaterial. In another example, injected polymer mixture 542 comprises adrug-polymer. In another example, injected polymeric mixture 542comprises a cap coating material.

Extruded stent coatings 540 are applied to stent framework 530 bypassing stent framework 530 through shaped orifice 554 of extrusion die550 to extrude polymeric mixture 542 onto at least a portion of stentframework 530. Polymeric mixture 542 may be extruded onto outer surface534 of stent framework 530, and may coat individual struts of stentframework 530 or cover stent framework 530 including apertures 536 withstent coating material.

Shaped orifice 554 may form a hole, with a diameter 556 correspondingwith the target outer diameter of stent coating 540. Stent frameworks530 are loaded onto mandrel or support wire 562, and pushed or pulledthrough shaped orifice 554 of extrusion die 550 to form an extrudedstent coating 540 on stent framework 530.

A heater 560 may be integrally formed with extrusion die 550 or wrappedaround extrusion die 550 to heat polymeric mixture 542 above anextrusion temperature when polymeric mixture 542 is being extrudedthrough shaped orifice 554.

Using additional extrusion die 550 with different diameters 556, primercoatings, drug-polymers, and cap coatings can be extruded onto stentframework 530 with multiple extrusion sequences, or combined withconventional dipping, brushing, spraying or painting sequences to formthe desired coating matrix. Additional processing may be performed oncoated stents to remove extruded polymeric mixture 542 from a pluralityof apertures within stent framework 530.

FIG. 6 shows a cross-sectional view of a system for coating a stent, inaccordance with another embodiment of the present invention at 600.Coating system 600 includes an extrusion die 650 having at least oneinlet port 652 and a shaped orifice 654. A polymeric mixture 642 isinjected through inlet port 652, through shaped orifice 654, and blownonto at least a portion of an inner surface 632 of a stent framework 630to apply a stent coating 640 onto stent framework 630. Shaped orifice654 typically forms a hole, with a diameter 656 corresponding with thetarget outer diameter of extruded stent coating 640. Stent framework 630is placed adjacent to shaped orifice 654 of extrusion die 650, andpolymeric mixture 642 is extruded through shaped orifice 654 onto atleast a portion of stent framework 630. Stent framework 630 may beplaced into a retaining tube 664 prior to extruding polymeric mixture642. An outer surface 634 of stent framework 630 contacts an innersurface 666 of retaining tube 664. Room temperature or hot gas 670 isblown through a gas injector port 672 onto extruded polymeric mixture642 to force extruded polymeric mixture onto stent framework 630.Polymeric mixture 642 may be extruded from extrusion die 650, and blownonto an inner surface 632 of stent framework 630 with gas 670 such aspre-heated nitrogen, argon or air. Alternatively, a vacuum may beapplied to force extruded polymeric mixture 642 onto stent framework630.

In one example, injected polymeric mixture 642 comprises a primercoating material. In another example, injected polymeric mixture 642comprises a drug-polymer. In another example, injected polymeric mixture642 comprises a cap coating material. Multiple passes through coatingsystem 600 may be used to apply multiple coatings or coatings withvarying constituency onto at least a portion of stent framework 630.

Polymeric mixture 642 comprises at least one polymer and may include oneor more therapeutic agents. Polymeric mixture 642, which is inserted asfeedstock into a commercial extrusion machine, is optionally heated andforced under pressure to extrude stent coating 640 onto stent framework630. Polymeric mixture 642 is injected into inlet port 652 of extrusiondie 650 using any conventional extrusion feed system such as a ram, ascrew, or a reciprocating plunger. A heater 660 may be integrally formedwith extrusion die 650 or wrapped around extrusion die 650 to heatpolymeric mixture 642 above an extrusion temperature when polymericmixture 642 is being extruded through shaped orifice 654.

With the same or additional extrusion die 650 with a different diameter656, various primer coatings, drug-polymers, and cap coatings can beextruded and blown onto stent framework 630 with multiple extrusionsequences, or combined with conventional dipping, brushing, spraying orpainting sequences to form the desired coating matrix. Additionalprocessing may be performed on coated stents to remove excess extrudedpolymeric mixture 642 from a plurality of apertures within stentframework 630.

FIG. 7 shows a flow diagram of a method for coating a stent, inaccordance with one embodiment of the current invention at 700. Stentcoating method 700 includes steps to extrude a coating such as a primercoating, a drug-polymer coating, or a cap coating onto a stent.

A stent framework is provided, as seen at block 705. The stent frameworkis generally tubular in geometry, with open ends and generally openapertures between struts and stent members that form the stentframework. The stent framework comprises a metallic or polymeric base,including a material such as stainless steel, nitinol, tantalum, MP35Nalloy, platinum, titanium, a chromium-based alloy, a cobalt-based alloy,a suitable biocompatible alloy, a suitable biocompatible material, abiocompatible polymer, or a combination thereof. The stent framework maybe bare or previously coated, and may be cleaned with various solvents,degreasers and cleansers to remove any debris, residues, or unwantedmaterials from the surface of the stent framework prior to extruding acoating.

The stent framework may be placed into a retaining tube or onto amandrel or support wire, as seen at block 710. Placement of the stentframework into the retaining tube allows an extruded coating to beextruded or blown onto at least an inner surface of the stent framework.Placement of the stent framework onto a mandrel or support wire allows astent coating to be extruded onto at least an outer surface of the stentframework as the stent framework and mandrel or wire is passed throughan extrusion die, and allows the stent frameworks to be individually fedinto an extruder or to be continuously or semi-continuously fed into theextruder.

A polymeric mixture including at least one polymer and optionally one ormore therapeutic agents is formed and fed into an extruder with theextrusion die, as seen at block 715. The polymeric mixture may comprise,for example, a primer coating material, a drug-polymer, or a cap coatingmaterial. In some cases, a suitable solvent is included in the polymericmixture. In other cases, the polymeric mixture is solvent-free. Theextrusion process allows polymers, drugs, and other therapeutic agentsto be hot-formed or cold-formed, using feedstock of various forms suchas powders, granules, spheres, pellets, beads, bars, rods and viscousliquids. Typically, the polymeric mixture is extruded without heating toretain the therapeutic agents in a preferred form. The extrusion ofcoatings at ambient temperatures allows a wide range of polymers andtherapeutic agents to be coated onto the stent framework. In some cases,the polymeric mixture may be heated above an extrusion temperature ofthe polymeric mixture to soften the polymers and to increase theflexibility of the mixture. The polymeric mixture may be pre-heated orheated when the polymeric mixture is extruded through a shaped orificeof the extrusion die with a heater that may be, for example, integrallyformed within the extrusion die or wrapped around the extrusion die.

The polymeric mixture is injected through at least one inlet port in theextrusion die, as seen at block 720. The polymeric mixture ispressurized and extruded through a shaped orifice of the extrusion dieonto at least a portion of the stent framework. The shaped orifice maycomprise, for example, an annulus with an inner diameter thatcorresponds to an inner diameter of the coated stent, and a larger outerdiameter that corresponds to an outer diameter of the coated stent. Inanother example, the shaped orifice comprises a hole with a diameterthat corresponds to the outer diameter of the coated stent.

In one embodiment, the stent framework is passed through the shapedorifice of the extrusion die, with the polymeric mixture being extrudedonto the stent framework to coat or jacket the stent, as seen at block725. The stent coating may be formed around the stent framework,encapsulating the stent framework. The polymeric mixture may be extrudedonto an inner surface of the stent framework, onto an outer surface ofthe stent framework, or both. One or more stent frameworks may be placedonto a mandrel or a support wire and fed through the extrusion die tocontinuously or semi-continuously coat the stents.

In another embodiment, the stent framework is placed into a retainingtube and positioned adjacent to the shaped orifice of the extrusion die,as seen at block 730. The stent framework may be placed into a retainingtube prior to the polymeric mixture being extruded onto the stentframework.

To form a coated stent, the polymeric mixture is extruded onto at leasta portion of the stent framework, as seen at block 735. The polymericmixture is extruded through the shaped orifice onto at least a portionof the stent framework.

With the stent framework placed adjacent to the shaped orifice, hot gassuch as nitrogen, argon or air may be blown onto the extruded polymericmixture, forcing the extruded polymeric mixture onto the stentframework, as seen at block 740. The gas may be at room temperature ormay be pre-heated to a temperature typically between room temperatureand the glass transition temperature of the polymeric mixture.

The extruded polymer mixture may be removed from a plurality ofapertures within the stent framework, as seen at block 745. Lasercutting, hot gas, and other techniques may be used for removing theextruded coating in selected areas such as the apertures.

Multiple coating steps may be employed to coat a stent, usingapplication techniques such as dipping, spraying, brushing, painting orextruding. Additional extruded coatings may be applied by repeating theaforementioned steps, which place additional coatings such as a cap coatand multiple drug-polymer layers, thereby increasing the quantity ofdrug delivered to the recipient. Drying steps or baking steps may beinterdispersed within the extrusion process steps to provide anyadditional cross-linking or curing of polymers that may be needed.

When the application of coatings is completed, the coated stent may becoupled to a delivery catheter. For example, the coated stent may berolled down to compress the stent framework against an inflatableballoon, which is positioned between the coated stent and the catheterfor deploying the coated stent in the body. In another example, aself-expanding coated stent may be placed inside a retractable sheathand coupled to the catheter body. Once the stent is inserted andpositioned in the body, the sheath can be retracted to deploy the coatedstent.

In one exemplary method, a fully processed coated stent is reduced indiameter and placed into the distal end of the catheter to form aninterference fit, which secures the stent onto the catheter. Thecatheter with the stent may be placed in a catheter package andsterilized prior to shipping and storing. Before clinical use, the stentis sterilized using any conventional medically accepted techniques.Sterilization may employ, for example, gamma-ray irradiation, e-beamradiation, ethylene oxide gas, or hydrogen peroxide gas plasmasterilization techniques.

When ready for deployment, the drug-polymer coated stent is insertedinto a vessel of the body. The drug-polymer coated stent is insertedtypically in a controlled environment such as a catheter lab orhospital. A delivery catheter, which helps position the drug-polymercoated stent in a vessel of the body, is usually inserted through asmall incision of the leg and into the femoral artery, and directedthrough the vascular system to a desired place in the vessel. Guidewires threaded through an inner lumen of the delivery catheter assist inpositioning and orienting the drug-polymer coated stent. The position ofthe drug-polymer coated stent may be monitored, for example, with afluoroscopic imaging system or an x-ray viewing system in conjunctionwith radiopaque markers on the coated stent, radiopaque markers on thedelivery catheter, or contrast fluid injected into an inner lumen of thedelivery catheter and into an inflatable catheter balloon that iscoupled to the drug-polymer coated stent. The stent is deployed, forexample, by expanding the stent with a balloon or by extracting a sheaththat allows a self-expandable stent to enlarge after positioning thestent at a desired location within the body. Prior to deployment,sterilization of the stent using conventional means is completed beforeclinical use. Once deployed within the body, one or more therapeuticagents that are included or interdispersed within the drug-polymercoating are eluted into the body to deliver their intended therapeuticbenefits.

While the embodiments of the invention disclosed herein are presentlyconsidered to be preferred, various changes and modifications can bemade without departing from the spirit and scope of the invention. Thescope of the invention is indicated in the appended claims, and allchanges that come within the meaning and range of equivalents areintended to be embraced therein.

What is claimed is:
 1. A coated stent comprising: a stent framework; andan extruded coating disposed on at least a portion of the stentframework, wherein the extruded coating encapsulates the stent frameworkand fills a plurality of apertures formed by the stent framework.
 2. Thestent of claim 1 wherein the stent framework comprises one of a metallicbase or a polymeric base.
 3. The stent of claim 1 wherein the stentframework comprises a material selected from the group consisting ofstainless steel, nitinol, tantalum, MP35N alloy, platinum, titanium, achromium-based alloy, a cobalt-based alloy, a suitable biocompatiblealloy, a suitable biocompatible material, a biocompatible polymer, and acombination thereof.
 4. The stent of claim 1 wherein the extrudedcoating comprises a primer coating.
 5. The stent of claim 1 wherein theextruded coating comprises a drug-polymer including at least onetherapeutic agent.
 6. The stent of claim 5 wherein the therapeutic agentis selected from the group consisting of an antirestenotic drug, ananti-cancer drug, an antisense agent, an antineoplastic agent, anantiproliferative agent, an antithrombogenic agent, an anticoagulant, anantiplatelet agent, an antibiotic, an anti-inflammatory agent, asteroid, a gene therapy agent, a therapeutic substance, an organic drug,a pharmaceutical compound, a recombinant DNA product, a recombinant RNAproduct, a collagen, a collagenic derivative, a protein, a proteinanalog, a saccharide, a saccharide derivative, a bioactive agent, apharmaceutical drug, and a combination thereof.
 7. The stent of claim 1wherein the extruded coating comprises a cap coating.